NM_018058.7:c.1432G>A

Variant names:

• chr10-97895299-C-T
• NM_018058.7:c.1432G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018058.7(CRTAC1):​c.1432G>A​(p.Asp478Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CRTAC1 NM_018058.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.78
• Publications: 0 publications found

Genes affected

CRTAC1 (HGNC:14882): (cartilage acidic protein 1) This gene encodes a glycosylated extracellular matrix protein that is found in the interterritorial matrix of articular deep zone cartilage. This protein is used as a marker to distinguish chondrocytes from osteoblasts and mesenchymal stem cells in culture. The presence of FG-GAP motifs and an RGD integrin-binding motif suggests that this protein may be involved in cell-cell or cell-matrix interactions. Copy number alterations in this gene have been observed in neurofibromatosis type 1-associated glomus tumors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018058.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAC1	NM_018058.7	MANE Select	c.1432G>A	p.Asp478Asn	missense	Exon 11 of 15	NP_060528.3
	CRTAC1	NM_001206528.3		c.1432G>A	p.Asp478Asn	missense	Exon 11 of 15	NP_001193457.1	Q9NQ79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAC1	ENST00000370597.8	TSL:1 MANE Select	c.1432G>A	p.Asp478Asn	missense	Exon 11 of 15	ENSP00000359629.3	Q9NQ79-1
	CRTAC1	ENST00000309155.4	TSL:1	c.1408G>A	p.Asp470Asn	missense	Exon 11 of 15	ENSP00000310810.3
	CRTAC1	ENST00000856696.1		c.1477G>A	p.Asp493Asn	missense	Exon 12 of 16	ENSP00000526755.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461442 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727022

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111980

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.38
Sift	Benign	0.16	T
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.92
MutPred		0.70		Gain of MoRF binding (P = 0.045)
MVP		0.85
MPC		1.1
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.31
gMVP		0.67
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr10-99655056;